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bioRxiv · 10.64898/2026.02.02.702263

Out with the Old: Contrasting Histone Marks are Associated with Dosage Compensation on the Ancient and New Z of a Moth with Complex Sex Chromosomes

Bett, V. K.·Elkrewi, M.·Macon, A.·Vicoso, B.
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Abstract

Sex chromosome differentiation is often accompanied by the evolution of dosage compensation (DC) mechanisms that balance gene expression between autosomes and sex chromosomes, and consequently between the sexes. ZW systems were traditionally thought to exhibit only partial DC, but recent studies in Lepidoptera, Artemia franciscana, and Apalone spinifera suggest a diverse range of compensation strategies, challenging traditional assumptions. While DC often involves chromatin-level regulation, the specific mechanisms in most ZW systems are still poorly understood. To explore these gaps, we generated a genome assembly of Cameraria ohridella (horse-chestnut leaf miner moth, Gracillidae), and combined transcriptomic data from two tissues with CUT&Tag epigenomic profiling targeting both active (H4K16ac, H3K4me3) and repressive (H3K27me3) chromatin marks. Our findings reveal a highly dynamic landscape of sex chromosome evolution in C. ohridella, including the ancestral Z (AncZ), a NeoZ1 formed by fusion of AncZ with an autosome, and a NeoZ2 that likely arose via the fusion of another autosome to the W chromosome. We uncover distinct dosage compensation (DC) patterns across ancestral and neo-sex chromosome regions. On the Ancestral Z, DC involves repression of gene expression in males (ZZ), with a depletion of the active histone mark H4K16ac being observed in this region. In contrast, NeoZ1 regions show upregulation of gene expression in the heterogametic sex (ZW), accompanied by enrichment of H4K16ac. Together, our findings underscore the dynamic nature of sex chromosome evolution and reveal variation in dosage compensation strategies across the Z chromosome, where the NeoZ1 appears to evolve entirely new, Drosophila-like mechanisms rather than co-opting the existing Nematode-like mechanisms of AncZ. We performed simulations that suggest that cooption of ancient DC mechanisms on a neo-sex chromosome is expected when it acts through up-regulation in the heterogametic sex but not when it involves downregulation in the homogametic sex, providing a framework for understanding the different patterns observed between Drosophila and Lepidoptera neo sex chromosomes.

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Bett, V. K., Elkrewi, M., Macon, A., Vicoso, B.. 2026-02-03. Out with the Old: Contrasting Histone Marks are Associated with Dosage Compensation on the Ancient and New Z of a Moth with Complex Sex Chromosomes. https://doi.org/10.64898/2026.02.02.702263

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